scholarly journals INFLUENCE OF NEVIRAPINE ON THE PHARMACODYNAMICS AND PHARMACOKINETICS OF REPAGLINIDE IN RATS AND RABBITS

Author(s):  
Sagarika Majhi ◽  
Lubhan Singh

Introduction: Management of HIV/AIDS is gradually expanding to include the chronic and metabolic complications and the adverse effects associated with its treatments like Type II diabetes mellitus. Repaglinide is a novel oral hypoglycemic agent chemically unrelated to sulphonylureas, metformin or acarbose used for the treatment of type II diabetes. Nevirapine is widely used non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection. Objective: The objective of this study was to examine the effect of oral administration of nevirapine on blood glucose and investigate their effect on the activity of repaglinide and to evaluate the safety and effectiveness of the combination. Materials and Methods: Studies in normal, diabetic rats and normal rabbits were conducted with oral doses of repaglinide, nevirapine and their combination. All the animals were fasted for 18 h prior to experimentation; during this period the animals were fed with water ad libitum. The blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8hours in rats by retro orbital puncture and by marginal ear vein puncture in rabbits at different time intervals. Further, the samples were analyzed for glucose by glucose oxidase/peroxidase (GOD/POD) method. The rabbit blood samples were analyzed by HPLC for serum repaglinide concentration. The serum repaglinide levels and pharmacokinetic parameters of repaglinide were evaluated with multiple dose treatments of nevirapine in rabbits. Result and Discussion: Nevirapine alone have no significant effect on the blood glucose level in rats and rabbits. Repaglinide produced hypoglycemic and antihyperglycemic activity in normal and diabetic rats with peak activity at 2 h and hypoglycemic activity in normal rabbits at 1.5 h. In combination, nevirapine reduced the effect of repaglinide in rats and rabbits. The interaction was found to be significant at both pharmacodynamic as well as at pharmacokinetic levels. Conclusion: Thus, it can be concluded that the combination of nevirapine and repaglinide may need dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. However, further studies are warranted.

2006 ◽  
Vol 291 (5) ◽  
pp. H2439-H2444 ◽  
Author(s):  
Danielle J. Padilla ◽  
Paul McDonough ◽  
Brad J. Behnke ◽  
Yutaka Kano ◽  
K. Sue Hageman ◽  
...  

Microcirculatory red blood cell (RBC) hemodynamics are impaired within skeletal muscle of Type I diabetic rats (Kindig CA, Sexton WL, Fedde MR, and Poole DC. Respir Physiol 111: 163–175, 1998). Whether muscle microcirculatory dysfunction occurs in Type II diabetes, the more prevalent form of the disease, is unknown. We hypothesized that Type II diabetes would reduce the proportion of capillaries supporting continuous RBC flow and RBC hemodynamics within the spinotrapezius muscle of the Goto-Kakizaki Type II diabetic rat (GK). With the use of intravital microscopy, muscle capillary diameter ( dc), capillary lineal density, capillary tube hematocrit (Hctcap), RBC flux ( FRBC), and velocity ( VRBC) were measured in healthy male Wistar (control: n = 5, blood glucose, 105 ± 5 mg/dl) and male GK ( n = 7, blood glucose, 263 ± 34 mg/dl) rats under resting conditions. Mean arterial pressure did not differ between groups ( P > 0.05). Sarcomere length was set to a physiological length (∼2.7 μm) to ensure that muscle stretching did not alter capillary hemodynamics; dc was not different between control and GK rats ( P > 0.05), but the percentage of RBC-perfused capillaries (control: 93 ± 3; GK: 66 ± 5 %), Hctcap, VRBC, FRBC, and O2 delivery per unit of muscle were all decreased in GK rats ( P < 0.05). This study indicates that Type II diabetes reduces both convective O2 delivery and diffusive O2 transport properties within muscle microcirculation. If these microcirculatory deficits are present during exercise, it may provide a basis for the reduced O2 exchange characteristic of Type II diabetic patients.


2019 ◽  
Vol 7 (1) ◽  
pp. 1-4
Author(s):  
Alekhya Ayalapuram

With changing lifestyle and increasing obesity, prevalence of type -II Diabetes Mellitus is increasing in geriatric individuals, who are generally prone to tooth loss. As a result the demand for implants in these patients is also increasing and planning implants has been a challenge to present day dentists. Diabetes Mellitus causes impaired metabolism in general, especially bone metabolism resulting in impaired Osseointegration and poor wound healing. Growing demand of implants in Type II DM patients has initiated research towards implants survival rates. Extensive research till now states - poorly controlled diabetic patients have higher implant failure rates, where as Diabetic patients with controlled blood glucose levels respond to implants in similar way as healthy patients. The present article is one such trail to confirm that type II Diabetes Mellitus is no more contra-indication for Implants till Blood glucose levels are controlled to normal levels. Key words: Type-II Diabetes Mellitus; Two-piece implant; Delayed loading;


2007 ◽  
Vol 135 (3-4) ◽  
pp. 143-146 ◽  
Author(s):  
Nada Kostic ◽  
Zorica Caparevic ◽  
Sanja Ilic

Introduction. Lipid peroxidation and antioxidant systems are important factors affecting the metabolism of lipoproteins in diabetes mellitus. Objective. The aim of this study was to investigate the lipid and antioxidant parameters in type II diabetes mellitus patients, and also to determine the effect of diabetic complications on these parameters. Method. Lipid status, Oxidized LDL cholesterol, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and plasminogen activator inhibitor (PAI-1) levels in plasma of 50 type II diabetic patients were measured with commercially available kits. Results. The results showed only statistically significant higher levels of triglycerides (3.12?3.9 mmol/l) in diabetics compared with the controls. Ox-LDL cholesterol (84.7?16.9 mmol/l) and SOD activities (913.4?120.3 U/gHb) in type 2 diabetes mellitus were higher than those of the controls, but there was no statistical significance. On the other hand, in patients with diabetes mellitus and complications, LDL cholesterol, PAI-1, SOD and GSH-Px activities were higher but not significantly than those without complications. Triglycerides and Ox-LDL cholesterol were lower in the group of diabetic patients with complications in comparison to the group without complications. Conclusion. These results indicate that antioxidant status may be affected in type II diabetic patients and that the rise in some enzyme activities could be a compensatory mechanism to prevent tissue damage. Our results suggest that the rise in PAI-1 in type II diabetics with complications may be a good marker of vascular endothelial dysfunction.


2021 ◽  
Vol 15 (7) ◽  
pp. 2317-2319
Author(s):  
Kashif Ali Samin ◽  
Khalil Ullah ◽  
Muhammad Ikram Shah ◽  
Abidamateen Ansari ◽  
Sadia Khalil ◽  
...  

Background and Aim: Morbidity and mortality from non-communicable diseases, particularly diabetes are increasing rapidly in Pakistan, the prevalence has reached 17.1%. A strong association has been witnessed between type II diabetes mellitus with atherosclerosis and serum uric acid level. The current study aim was to assess the levels of serum uric acid in type II diabetes mellitus. Materials and Methods: This cross-sectional study was carried out on 85 diagnosed patients of type II diabetes mellitus in Diabetes hospital, Peshawar and the Department of General Medicine, Shaikh Zayed Medical Complex, Lahore during the period from March 2020 to August 2020.Type II diabetes mellitus (DM) diagnosed patients 85 and healthy control 30 were evaluated in this study. The level of hyperuricemia was defined for women > 6 mg/dl and men >7 mg/dl in men. Results: In this study, a total of 85 diabetic diagnosed patients and 30 healthy controls were enrolled. No significant differences were there in the baseline characteristics like anthropometric and socio-demographic parameters. The mean age for diagnosed and control cases was 58.6±8.7 and 56.5±7.6 years with an age range of 40 and 80 years. Hyperuricemia proportion among diabetic patients was 12.13% while none of the control cases had hyperuricemia. The uric acid means level increased from 4.29±0.81 mg/dl with a diabetic duration between 3 and 4 years to 4.59±0.99 mg/dl with a diabetic duration of 5 to 7 years. Furthermore, mean serum uric acid level reached 6.50±1.08 in cases with diabetic duration 8 to 12 years. Statistically, a significant association was found between diabetic duration and serum uric acid. Also, a positive correlation was found in hyperlipidemia, serum uric acid levels, and hypertension. Conclusion: In diabetic patients serum uric acid levels were found to be significantly higher. Diabetic patients had hypertension, elevated serum uric acid levels, and high triglycerides with dyslipidemia. The rise in serum uric acid levels is proportional to the duration of diabetes. Keywords: Serum uric acid, Type 2 diabetes mellitus, Hypertension


2021 ◽  
Vol 11 (6) ◽  
pp. 1138-1143
Author(s):  
Fang Ma ◽  
Jimei Xu ◽  
Weiwei Yang ◽  
Fuqin Bian

In this study, extreme velocity ultrasonic imaging pulse wave technology was used to detect the main indices of atherosclerosis such as carotid intima-media thickness (IMT) and carotid elasticity, and biochemical indices such as glycated hemoglobin, blood glucose and blood lipids in one hundred twenty 18–60-year-old patients with type II diabetes mellitus (T2DM) and 120 healthy controls. We analyzed the correlations between carotid elasticity, carotid IMT, and a range of biochemical indices. The results indicated that when the carotid IMT in young and middle-aged patients with T2DM was within the normal range (0.56±0.03 mm), the carotid artery elasticity was abnormal [Pulse wave propagation velocity (PWV)-BS = 7.69± 1.26 m/s; PWV-ES = 8.34±1.51 m/s; P < 0.05]. Additionally, PWV-BS was positively correlated with age, course of the disease, glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) (r = 0.297, 0.377, 0.369, 0.382), and PWV-ES was positively correlated with age, course of the disease, HbA1c, and FBG (r = 0.318, 0.386, 0.392, 0.339). This finding provides a basis for extreme velocity ultrasonic imaging pulse wave technology to become a new method for the early screening of atherosclerosis in patients with T2DM; this is important for timely clinical intervention in patients with T2DM.


2017 ◽  
Vol 2 (2) ◽  
pp. 26-34
Author(s):  
Hridaya Parajuli ◽  
Jyotsna Shakya ◽  
Bashu Dev Pardhe ◽  
Puspa Raj Khanal ◽  
Narayan Prasad Parajuli ◽  
...  

Background: Hyperuricemia is associated with type 2 diabetes, which is a metabolic disorder of multiple etiologies resulting from defects in insulin action. The present study wascarried out to look for any association between uric acid and Type II Diabetes Mellitus and also status of triacylglycerol level among those patients.Methods: The blood samples were collected 100 diabetic and 100 non-diabetic individuals in the department of biochemistry and then analyzed for estimation of blood glucose, Uric Acid and Triacylglycerol level.Results: The average level of serum uric acid in diabetic patients was higher (5.706±1.617) in comparison to non diabetic subjects (4.322±0.784) with statistically significant difference (p≤0.05). For female the result indicate there was a positive correlation between (FBS and triglycerides) and (triglycerides and uric acids) which was statistically significant (r =-0.465, n = 41, p = 0.002) and(r =-0.370, n = 41, p = 0.017) respectively.Conclusions: This study documents that hyperuricemia is associated with type 2 diabetes mellitus. Furthermore, the serum triacylglycerol and serum uric acid is also found to be associated risk factors for diabetic complications. Hence, timely diagnosis and management of diabetes is vital to control the complications related to diabetes.Ann. Clin. Chem. Lab. Med. 2016:2(1); 26-34


2018 ◽  
Vol 08 (01) ◽  
pp. 11-14
Author(s):  
Aditya Mungamuri ◽  
Sunil Kumar Y. ◽  
Suchetha Kumari N. ◽  
Ullal Harshini Devi

Abstract Background: Diabetes Mellitus (DM) has become an epidemic in the 21st century where India leads the world with largest number of patients. There is increasing evidence that inflammation is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidaemia and atherosclerosis. Many previous studies indicate inflammatory markers like CRP, IL-6, IL-8, TNF-alpha, fibrinogen, total sialic acid, ceruloplasmin and total leucocyte count (TLC) are raised in Type II Diabetes Mellitus. However, not many studies have done association of ESR and TLC in DM. Aims: In the present study inflammatory markers like CRP, total leukocyte count and ESR were compared in diabetic and non-diabetic patients. Materials and Methods: 5mL of venous blood was taken from the study subjects.CRP, TLC and ESR was estimated. Results: There was a significant rise in the CRP, TLC and ESR values seen in patients diagnosed with type II diabetes mellitus when compared to normal individuals. All three parameters (CRP, TLC, and ESR) were raised in a total of 7 cases (14%). 14 cases (28%) showed elevated levels of both CRP and ESR. A significant 8 cases (16%) showed elevation of CRP alone. There was a rise of ESR alone in 5 cases (10%). Conclusion: CRP, TLC and ESR are elevated in diabetic patients in comparison to normal individuals. These increase the risk of diabetic related complications like atherosclerosis and dyslipaedemia. Hence, anti-inflammatory drugs in combination with antidiabetic treatment can delay these complications.


2004 ◽  
Vol 82 (10) ◽  
pp. 888-894 ◽  
Author(s):  
Tod A Clark ◽  
Andrea L Edel ◽  
Clayton E Heyliger ◽  
Grant N Pierce

A novel black tea decoction containing vanadate has successfully replaced insulin in a rat model of insulin-dependent diabetes but is untested in non-insulin-dependent diabetic animals. A tea-vanadate decoction (TV) containing 30 or 40 mg sodium orthovanadate was administered by oral gavage to two groups of Zucker diabetic fatty rats and a conventional water vehicle containing 30 or 40 mg of sodium orthovanadate to two others. In the latter group receiving the 30-mg dose, vanadate induced diarrhea in 50% of the rats and death in 10%. In contrast, TV-treated rats had no incidence of diarrhea and no deaths. Symptoms were more severe in both groups with higher vanadate doses, so these were discontinued. After ~16 weeks, the level of vanadium in plasma and tissue extracts was negligible in a further group of untreated rats but highly elevated after vanadate treatment. Vanadium levels were not significantly different between the TV-treated diabetic rats and the diabetic rats given vanadate in a water vehicle. Over the 115 days of the study, blood glucose levels increased from ~17 to 25 mmol/L in untreated diabetic rats. This was effectively lowered (to <10 mmol/L) by TV treatment. Fasting blood glucose levels were 5, 7, and 20 mmol/L in control (nondiabetic, untreated), TV-treated and untreated diabetic rats, respectively. Rats required treatment with TV for only ~50% of the days in the study. Increase in body mass during the study was significantly lower in untreated diabetic rats (despite higher food intake) than the other groups. Body mass gain and food intake were normal in TV-treated rats. Water intake was 28 mL/rat daily in control rats, 130 mL/rat daily in untreated diabetic rats, and 52 mL/rat daily in TV-treated diabetic rats. Plasma creatinine and aspartate aminotransferase levels were significantly depressed in untreated diabetic rats, and TV treatment normalized this. Our results demonstrate that a novel oral therapy containing black tea and vanadate possesses a striking capacity to regulate glucose and attenuates complications in a rat model of type II diabetes. Key words: diabetes mellitus, tea, glycemia, type II diabetes.


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